Pharmaceutical Technology Europe - June 2012 - (Page 11)

Freeze-Drying Process Optimisation for a Small Molecule: Hennning Gieseler and Susanne Hibler evaluate the thermal properties of a gentamicin sulphate as a small-molecule model drug in optimising the freeze-drying cycle. The best approach to an optimised freeze-drying cycle is the reduction of primary drying time because this phase is commonly the most time-consuming part. To follow this approach, an accurate and representative measurement of the critical formulation temperature (CFT) is required, which poses the upper boundary for the product temperature at the sublimation interface (Tp) during primary drying. With regard to process time and product-quality attributes, such as elegant-cake appearance, low residual moisture, quick and complete reconstitution and drug activity, the product temperature over time profile during primary drying should be close to but below the CFT (2-4). In some cases, however, drying in the microcollapse regime is possible without severe structural loss, as reported for protein formulations, and could also be a promising approach to further process optimisation for small molecule drugs. In a study, the thermal properties of gentamicin sulphate as a small-molecule model substance were characterised by means of freeze-dry microscopy (FDM) and differential scanning calorimetry (DSC) to determine the CFT at different concentrations and to investigate the potential for further freeze-drying cycle optimisation. were prepared with deionised water. The glass-transition temperature of the maximally freeze-concentrated solute (Tg´) for the 5% (w/v) gentamicin sulphate solution was determined using a differential scanning calorimeter. Collapse temperatures (Tc) for the 2, 5, 10, 20 and 30% (w/v) sample solutions were investigated directly after preparation and after one week of storage at room temperature. The FDM equipment consisted of a microscope with a polariser, a lambda disk and a freeze-drying stage. The results of this study show that even for the relatively simple solution of a pure small-molecule drug, the collapse temperature determined by FDM can be considered as the practically more relevant CFT for process development and optimisation. The direct observation of the collapse event and the width of the gap between Toc and Tfc can provide additional valuable information on the temperature tolerance of the sample. PTE Henning Gieseler is an assistant professor and group leader at the University of Erlangen and managing director of Gilyos GmbH. Susanne Hibler is a graduate student at the University of Erlangen. Read the full study at: PharmTech.com/HGieseler Methods The pure gentamicin sulphate drug substance used for the thermal characterisation was provided by Merck KGaA. Gentamicin sulphate solutions of 2, 5, 10, 20 and 30% (w/v) 2 Analytical Stability 11 Freeze Drying Optimisation 3 Aseptic Filling 12 Hot Melt Extrusion 4 News 14 Interview 10 Manufacturing 16 Ask the Expert http://www.PharmTech.com/HGieseler

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - June 2012

Pharmaceutical Technology Europe - June 2012
Contents
Analytical Stability
Aseptic Filling
News
Blogs Abridged
Cleaning
Manufacturing
Freeze Drying Optimisation
Hot Melt Extrusion
Column Crunch: Biomanufacturing; European Regulators Struggle
Interview
Ask the Expert

Pharmaceutical Technology Europe - June 2012